Please use this identifier to cite or link to this item:
Title: MBNL1 and PTB cooperate to repress splicing of Tpm1 exon 3
Authors: Gooding, C.
Edge, C.
Lorenz, M.
Coelho, M. B.
Winters, M.
Kaminski, C. F.
Cherny, Dmitry
Eperon, Ian C.
Smith, C. W.
First Published: 19-Mar-2013
Publisher: Oxford University Press
Citation: Nucleic Acids Research, 2013, 41 (9), pp. 4765-4782
Abstract: Exon 3 of the rat α-tropomyosin (Tpm1) gene is repressed in smooth muscle cells, allowing inclusion of the mutually exclusive partner exon 2. Two key types of elements affect repression of exon 3 splicing: binding sites for polypyrimidine tract-binding protein (PTB) and additional negative regulatory elements consisting of clusters of UGC or CUG motifs. Here, we show that the UGC clusters are bound by muscleblind-like proteins (MBNL), which act as repressors of Tpm1 exon 3. We show that the N-terminal region of MBNL1, containing its four CCCH zinc-finger domains, is sufficient to mediate repression. The same region of MBNL1 can make a direct protein-to-protein interaction with PTB, and RNA binding by MBNL promotes this interaction, apparently by inducing a conformational change in MBNL. Moreover, single molecule analysis showed that MBNL-binding sites increase the binding of PTB to its own sites. Our data suggest that the smooth muscle splicing of Tpm1 is mediated by allosteric assembly of an RNA-protein complex minimally comprising PTB, MBNL and their cognate RNA-binding sites.
DOI Link: 10.1093/nar/gkt168
ISSN: 0305-1048
eISSN: 1362-4962
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Biochemistry

Files in This Item:
File Description SizeFormat 
MBNL1 and PTB cooperate to repress splicing of Tpm1 exon 3..pdfPublished (publisher PDF)5.29 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.